This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This program project is a collaborative study with Dr. Lieberman (Harvard) to develop an effective microbicide based on small interfering RNA (siRNA) technology. We are also developing a model of herpesvirus transmission to determine if this can also be used to develop preventative microbicides. Since genital herpes is associated with markedly increased rates of HIV transmission, and since genital herpes infects over 20% of adolescents/adults, this approach is also in line with our goals to reduce HIV transmission. We have now generated a large scale HSV-2 stock for use in NHP challenge experiments which will begin in February. We will also start testing siRNAs against CD45 and nectin to reduce inflammation and mask HSV-2 receptors respectively in vivo.